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S004
Trypanosoma cruzi interaction with host integrins and
calcium channels stimulates microvesicle release to allow
cell entry
Ephraim A. Ansa-Addo and Jameel M. Inal
London Metropolitan University, London, United Kingdom
Chagas disease, the debilitating infection caused by the intracellular parasite, Trypanosoma cruzi, affects approximately 16 to 18
million individuals in Latin America and leads to about 50, 000
deaths per annum. Host microvesicles (MVs) help pathogens, such
as the intracellular parasite, T. cruzi, evade complement attack.
We have now found that the infectious metacyclic trypomastigote
forms, by interacting with host integrins, lipid rafts and stretch
activated channels, stimulate a calcium-mediated depolymerisation of the actin cytoskeleton, and MV release. The release of MVs
in turn stimulates a lysosomal repair mechanism in the host cell,
to plug the breach in the plasma membrane. By using specific
inhibitors of lysosomal exocytosis and both pharmacological and
siRNA-mediated inhibition of microvesicle release, we describe
a novel entry mechanism by which the parasite opportunistically takes advantage of a host membrane repair mechanism,
to execute entry before membrane integrity is fully restored. Our
knowledge of this mechanism, and that its abrogation leads to
reduced infection, is likely to lead to future potential therapies, for
several increasingly important infectious diseases.